crossing96/oncoscreening huggingface dataset:
Robot-assisted Radical Cystectomy with Orthotopic Neobladder Reconstruction: Techniques and Functional Outcomes in Males.	BACKGROUND: Little is known regarding functional outcomes after robot-assisted radical cystectomy (RARC) and intracorporeal neobladder (ICNB) reconstruction. OBJECTIVE: To report on urinary continence (UC) and erectile function (EF) at 12 mo after RARC and ICNB reconstruction and investigate predictors of these outcomes. DESIGN, SETTING, AND PARTICIPANTS: We used data from a multi-institutional database of patients who underwent RARC and ICNB reconstruction for bladder cancer. SURGICAL PROCEDURE: The cystoprostatectomy sensu stricto followed the conventional steps. ICNB reconstruction was performed at the physician's discretion according to the Studer/Wiklund, S pouch, Gaston, vescica ileale Padovana, or Hautmann technique. The techniques are detailed in the video accompanying the article. MEASUREMENTS: The outcomes measured were UC and EF at 12 mo. RESULTS AND LIMITATIONS: A total of 732 male patients were identified with a median age at diagnosis of 64 yr (interquartile range 58-70). The ICNB reconstruction technique was Studer/Wiklund in 74%, S pouch in 1.5%, Gaston in 19%, vescica ileale Padovana in 1.5%, and Hautmann in 4% of cases. The 12-mo UC rate was 86% for daytime and 66% for nighttime continence, including patients who reported the use of a safety pad (20% and 32%, respectively). The 12-mo EF rate was 55%, including men who reported potency with the aid of phosphodiesterase type 5 inhibitors (24%). After adjusting for potential confounders, neobladder type was not associated with UC. Unilateral nerve-sparing (odds ratio [OR] 3.85, 95% confidence interval [CI] 1.88-7.85; p < 0.001) and bilateral nerve-sparing (OR 6.25, 95% CI 3.55-11.0; p < 0.001), were positively associated with EF, whereas age (OR 0.93, 95% CI 0.91-0.95; p < 0.001) and an American Society of Anesthesiologists score of 3 (OR 0.46, 95% CI 0.25-0.89; p < 0.02) were inversely associated with EF. CONCLUSIONS: RARC and ICNB reconstruction are generally associated with good functional outcomes in terms of UC. EF is highly affected by the degree of nerve preservation, age, and comorbidities. PATIENT SUMMARY: We investigated functional outcomes after robot-assisted removal of the bladder in terms of urinary continence and erectile function. We found that, in general, patients have relatively good functional outcomes at 12 months after surgery.	bladder
The Efficacy and Safety of Tislelizumab as Adjuvant Treatment for Advanced or Metastatic Bladder Cancer in People Living With HIV: A Retrospective Multi-Center Study.	BACKGROUND: People living with HIV (PLWH) have a worse prognosis than the general population. Locally advanced or metastatic bladder cancer (BCa) in PLWH has gradually been increasing in recent years. Immune checkpoint inhibitors can improve antitumor activity in the general population, but relevant data in PLWH are unknown. We thus evaluated the efficacy and safety of tislelizumab in PLWH with locally advanced or metastatic BCa. METHODS: This retrospective study included 24 patients with locally advanced or metastatic BCa, both HIV positive or negative who underwent tislelizumab treatment (200 mg i.v. every 3 weeks, Q3W) from the multi-centers between December 2019 and March 2022. Demographic details, clinical data, and cancer status were collected. The overall survival (OS), progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), and treatment-related adverse events (TRAEs) were recorded and evaluated. RESULTS: A total of 24 individuals were chosen for this study, 10 had HIV and the other 14 did not. The median OS in the HIV-negative group was 62.3 (95% CI, 52.6 to 72.2) was no longer than that of the PLWH group 41.9 (95% CI, 32.9 to 51.0) weeks (HR .7, [95% CI, .17 to 3.30], P = .70). Furthermore, the median PFS in the HIV-negative group was 50.0 (95% CI, 36.2 to 63.9) was also no longer than that of the PLWH group 35.9 (95% CI, 25.5 to 46.3) (HR, 1.34, [95% CI, .38 to 4.69], P = .63). Of 24 patients, treatment-related adverse events, grade 3 or 4 occurred in 2 in the PLWH group and 3 in the HIV-negative group. CONCLUSION: This retrospective multi-center study suggested that tislelizumab may provide encouraging antitumor activity and could be generally well tolerated. In this retrospective analysis of patients with locally advanced or metastatic BCa, it seems that PLWH may have similar overall and progression-free survival compared to HIV-negative cases.	bladder
[Tumor cell-based glycolytic metabolism and single-cell sequencing of urinary exfoliated cells for the diagnosis and molecular profiling of urothelial carcinoma].	Objective: To explore the diagnostic values of HK2 testing and single-cell sequencing in the urothelial carcinoma (UC). Methods: The qualified urine specimens of 265 suspected UC patients or postoperative patients from the Cancer Hospital of Chinese Academy of Medical Sciences, Beijing, China were collected. Both exfoliative cytology and HK2 testing were performed on clinically suspected UC or postoperative patients. The performance of diagnostic cytology and HK2, including consistency, sensitivity, specificity, positive predictive value and negative predictive value, was evaluated based on histopathological, clinical and imaging diagnosis. Isolated HK2 metabolically abnormal cells were subject to single-cell sequencing to verify the reliability of HK2 detection performance and to explore the molecular characteristics of UC. Results: The concordance rate of HK2 testing and cytology for detecting UC was 90.3% (102/113, Kappa=0.604). Compared with cytology, the sensitivity of HK2 was significantly higher (85.2% versus 75.6%, P=0.024). The detection sensitivity of combined HK2 testing and cytology was increased to 91.1%. HK2 testing was significantly more sensitive than cytology for diagnosing UC in the upper urinary tract (81.8% versus 65.5%, P=0.022). It was also more sensitive than cytology for diagnosing early-stage UC (82.6% versus 69.5%, P=0.375) and low-grade UC (69.6% versus 47.8%, P=0.125). Single-cell sequencing of the ten patients, whose samples were positive for HK2, demonstrated highly concordant copy number variations (CNVs) in tumor cells from the same UC patient, with heterogeneity in CNV profiles among different patients. Deletion of chromosome 8p was found in 3 of the 4 urine samples of renal pelvis UC. The 2 patients with benign lesions had no CNVs in all sequenced cells. Conclusions: The test for abnormal urinary glycolytic HK2 metabolism can assist urine cytology to improve the sensitivity of UC diagnosis, and it provides a novel and reliable approach for early detection of upper urinary tract UC and lower grade UC. Meanwhile, this study has preliminarily revealed the feasibility of single-cell sequencing in urinary samples, which is expected to improve the diagnostic specificity of HK2 testing.	bladder
DNA polymerase POLD1 promotes proliferation and metastasis of bladder cancer by stabilizing MYC.	To date, most studies on the DNA polymerase, POLD1, have focused on the effect of POLD1 inactivation mutations in tumors. However, the implications of high POLD1 expression in tumorigenesis remains elusive. Here, we determine that POLD1 has a pro-carcinogenic role in bladder cancer (BLCA) and is associated to the malignancy and prognosis of BLCA. Our studies demonstrate that POLD1 promotes the proliferation and metastasis of BLCA via MYC. Mechanistically, POLD1 stabilizes MYC in a manner independent of its' DNA polymerase activity. Instead, POLD1 attenuates FBXW7-mediated ubiquitination degradation of MYC by directly binding to the MYC homology box 1 domain competitively with FBXW7. Moreover, we find that POLD1 forms a complex with MYC to promote the transcriptional activity of MYC. In turn, MYC increases expression of POLD1, forming a POLD1-MYC positive feedback loop to enhance the pro-carcinogenic effect of POLD1-MYC on BLCA. Overall, our study identifies POLD1 as a promotor of BCLA via a MYC driven mechanism and suggest its potential as biomarker for BLCA.	bladder
STIL/AURKA axis promotes cell proliferation by influencing primary cilia formation in bladder cancer.	BACKGROUND: The primary cilia (PC) is a microtubule-based and nonmotile organelle which protrudes from the surface of almost all mammalian cells. At present, PC has been found to be a deficiency or loss in multiple cancers. Restoring PC could be a novel targeting therapy strategy. Our research showed that PC was reduced in human bladder cancer (BLCA) cells, and PC deficiency promotes cell proliferation. However, the concrete mechanisms remain unknown. SCL/TAL1 interrupting locus (STIL), a PC-related protein, was screened in our previous study and could influence the cell cycle by regulating PC in tumor cells. In this study, we aimed to elucidate the function of STIL for PC to explore the underlying mechanism of PC in BLCA. METHODS: Public database analysis, western blot, and enzyme-linked immunosorbent assay (ELISA) were used to screen genes and explore gene expression alteration. Immunofluorescence and western blot were utilized to investigate PC. Wound healing assay, clone formation assay, and CCK-8 assay were used to explore cell migration, growth, and proliferation. The co-immunoprecipitation and western blot were employed to reveal the interaction of STIL and AURKA. RESULTS: We found that high STIL expression is correlated with poor outcomes of BLCA patients. Further analysis revealed that STIL overexpression could inhibit PC formation, activate SHH signaling pathways, and promote cell proliferation. In contrast, STIL-knockdown could promote PC formation, inactivate SHH signaling, and inhibit cell proliferation. Furthermore, we found that the regulatory functions of STIL for PC depend on AURKA. STIL could influence proteasome activity and maintain AURKA stabilization. AURKA-knockdown could reverse PC deficiency caused by STIL overexpression for PC in BLCA cells. We observed that co-knockdown in STIL and AURKA significantly enhanced PC assembly. CONCLUSION: In summary, our result provides a potential therapy target for BLCA based on the restoration of PC.	bladder
Efficacy and Tolerability of Second-line Pembrolizumab With Radiation Therapy in Advanced Urothelial Carcinoma.	BACKGROUND/AIM: Considering the limited data available on immune checkpoint inhibitors and radiation combination therapy in advanced urothelial carcinoma, this study evaluated the survival benefit and associated toxicity of adding radiation therapy to second-line pembrolizumab. PATIENTS AND METHODS: We retrospectively examined 24 consecutive patients with advanced bladder or upper urinary tract urothelial carcinoma and for whom second-line pembrolizumab was initiated between August 2018 and October 2021 in combination with radiation therapy (with curative intent in 12 patients, and palliative intent in 12 patients). Their survival outcomes and toxicities were compared with those of propensity-score-matched cohorts from a Japanese multicenter study with similar characteristics who received pembrolizumab monotherapy. RESULTS: The median follow-up periods after pembrolizumab initiation were 15 months for the curative cohort and 4 months for the palliative cohort. The median overall survival was 27.7 months for the curative cohort and 4.8 months for the palliative cohort. Compared with the matched pembrolizumab monotherapy cohort, overall survival was better among the curative cohort although not statistically significant (p=0.13), but similar between the palliative and matched pembrolizumab monotherapy cohorts (p=0.44). There was no difference in the incidence of grade ≥2 adverse events between the combination and monotherapy cohorts, irrespective of the intent of radiation therapy. CONCLUSION: The combination of radiation therapy and pembrolizumab can be performed with a clinically acceptable safety profile, and the addition of radiation therapy to immune checkpoint inhibitors may improve survival outcome after pembrolizumab treatment in cases where the intent of radiation therapy is curative.	bladder
Impact of smoking on urologic cancers: a snapshot of current evidence.	PURPOSE: The purpose of this paper is to present evidence regarding the associations between smoking and the following urologic cancers: prostate, bladder, renal, and upper tract urothelial cancer (UTUC). METHODS: This is a narrative review. PubMed was queried for evidence-based analyses and trials regarding the associations between smoking and prostate, bladder, renal, and UTUC tumors from inception to September 1, 2022. Emphasis was placed on articles referenced in national guidelines and protocols. RESULTS: Prostate-multiple studies associate smoking with higher Gleason score, higher tumor stage, and extracapsular invasion. Though smoking has not yet been linked to tumorigenesis, there is evidence that it plays a role in biochemical recurrence and cancer-specific mortality. Bladder-smoking is strongly associated with bladder cancer, likely due to DNA damage from the release of carcinogenic compounds. Additionally, smoking has been linked to increased cancer-specific mortality and higher risk of tumor recurrence. Renal-smoking tobacco has been associated with tumorigenesis, higher tumor grade and stage, poorer mortality rates, and a greater risk of tumor recurrence. UTUC-tumorigenesis has been associated with smoking tobacco. Additionally, more advanced disease, higher stage, lymph node metastases, poorer survival outcomes, and tumor recurrence have been linked to smoking. CONCLUSION: Smoking has been shown to significantly affect most urologic cancers and has been associated with more aggressive disease, poorer outcomes, and tumor recurrence. The role of smoking cessation is still unclear, but appears to provide some protective effect. Urologists have an opportunity to engage in primary prevention by encouraging cessation practices.	bladder
Photodynamic cystoscopy for bladder cancer diagnosis and for NMIBC follow-up: An overview of systematic reviews and meta-analyses.	INTRODUCTION: Currently, bladder cancer detection is based on cytology and cystoscopy. White light cystoscopy (WLC) is an invasive procedure and may under-detect flat lesions. Blue light cystoscopy (BLC) and narrow band imaging (NBI) cystoscopy are new modalities that could improve the detection of non-muscle invasive bladder cancer (NMIBC) and its recurrence or progression to muscle invasive bladder cancer. We present a systematic review on BLC and NBI cystoscopy for bladder cancer diagnosis and NMIBC follow-up. MATERIAL AND METHODS: All available systematic reviews and meta-analyses on cystoscopy published in PubMed® between May 2010 and March 2021 were identified and reviewed. The main endpoints were clinical performance for bladder cancer diagnosis and for recurrence or progression detection during NMIBC follow-up, and additional value compared with cytology and/or WLC. RESULTS: Most of the meta-analyses and systematic reviews published suggest a better sensitivity of BLC and NBI cystoscopy compared to WLC, particularly for the detection of flat lesions (CIS). NBI- and BLC-guided TURBT could decrease the recurrence rates. However, their clinical utility to reduce progression rate and increase survival is still unclear. CONCLUSIONS: BLC and NBI cystoscopy are efficient techniques for bladder cancer diagnosis and NMIBC follow-up. However, their clinical benefit remains to be confirmed.	bladder
NEDD4L inhibits migration, invasion, cisplatin resistance and promotes apoptosis of bladder cancer cells by inactivating the p62/Keap1/Nrf2 pathway.	PURPOSE: This study identified the function of neural precursor cell expressed developmentally down-regulated 4-like (NEDD4L) on bladder cancer (BLCA). METHODS: NEDD4L expression in BLCA patients was scrutinized. The function of NEDD4L on the viability, apoptosis, migration and invasion of BLCA cells was evaluated by cell counting kit-8, flow cytometry and Transwell assays. The effect of NEDD4L on the cisplatin (DDP) resistance of the DDP-resistant BLCA cells was explored. The influence of NEDD4L on the p62/Keap1/Nrf2 pathway activity in BLCA cells was tested by Western blot. Rescue experiments were implemented to verify whether NEDD4L regulated BLCA cell malignant behavior by mediating the Keap1/Nrf2 pathway activity via p62. The effect of NEDD4L on the growth and the p62/Keap1/Nrf2 pathway activity in vivo was researched in xenograft tumor nude mice models. RESULTS: The down-regulated NEDD4L in BLCA patients was associated with unfavorable survival. NEDD4L suppressed the viability (inhibition rate 57.1%/49.0%), migration (inhibition rate 49.7%/77.1%), invasion (inhibition rate 50.6%/75.7%), promoted the apoptosis of T24/5637 cells (promotion rate 243.8%/201.9%), reduced IC 50 of DDP-resistant T24/5637 cells from 132.2/101.8 to 57.81/59.71 μM, respectively, and inactivated the p62/Keap1/Nrf2 pathway in T24/5637 cells. p62 up-regulation partially abrogated the inhibition of NEDD4L on the Keap1/Nrf2 pathway activity, the malignant behavior of BLCA cells, and the DDP resistance of DDP-resistant BLCA cells. NEDD4L overexpression inhibited the tumor growth and the p62/Keap1/Nrf2 pathway activity in vivo in BLCA. CONCLUSION: NEDD4L inhibits the progression of BLCA by inactivating the p62/Keap1/Nrf2 pathway. It may be an effective target for BLCA treatment.	bladder
[Intravesical instillation of bacillus Calmette-Guerin for non-muscle invasive bladder cancer: outcomes of 421 patients in a single center].	OBJECTIVE: To assess the therapeutic effect and adverse effect of intravesical instillation of bacillus Calmette-Guerin (BCG) for treatment of non-muscle invasive bladder cancer (NMIBC) and analyze the independent predictors of patient survival. METHODS: We retrospectively collected the clinical data from 421 patients (mean age 61.79±11.51 years) with NMIBC, who received intravesical instillation of BCG after surgery in Sun Yat-sen University Cancer Center from September, 2015 to September, 2021. Recurrence-free survival (RFS), progression-free survival (PFS), and disease specific survival (DSS) of the patients were analyzed, and the adverse effects were assessed using Common Terminology Criteria for Adverse Events 5.0. Kaplan-Meier analysis, univariate and multivariate COX regression analyses were used to identify the independent predictors of the patients' survival outcomes. RESULTS: The median follow-up of the patients was 17 months, during which 88 (20.9%) patients experienced recurrence (median time to recurrence of 10 months, range 3-58 months); 40 (9.5%) patients showed tumor progression (median time to progression of 18 months, range 3-50 months); and 14 (3.3%) patients died (median survival time of 30 months, range 8-52 months). Adverse events of grade 1, 2, and 3 occurred in 69, 110, and 23 of the patients, respectively. Survival analysis indicated that an age below 67.5 years (P=0.013), first tumor onset (P < 0.001), solitary tumor (P= 0.010), time to recurrence over one year (P=0.042), low levels of neutrophils (P=0.005), monocytes (P=0.005) and neutrophil/lymphocyte ratio (NLR; P=0.014), and cytokeratin 19 fragment 21-1 (CyFra21-1; P=0.002) were all associated with a higher PFS rate. Multivariate COX analysis suggested that the time of tumor recurrence (P=0.007, HR=2.669, 95% CI: 1.316-5.414), monocyte counts (P=0.015, HR=0.376, 95% CI: 0.171-0.829), and serum CyFra21-1 level (P=0.002, HR=0.312, 95% CI: 0.151-0.647) were independent predictors of RFS; primary tumor or tumor relapse (P=0.003, HR=0.301, 95% CI: 0.138-0.660), neutrophil counts (P=0.028, HR=0.302, 95% CI: 0.103-0.882), and CyFra21-1 level (P=0.029, HR=0.358, 95% CI: 0.142-0.903) were independent predictors of PFS following BCG instillation. CONCLUSION: Intravesical instillation of BCG is effective for treatment of intermediate or high-risk NMIBC, and the adverse effects are tolerable in most cases. The time of tumor recurrence, monocyte counts, and serum CyFra21-1 level are independent predictors of RFS, and primary tumor or tumor relapse, neutrophil counts, and CyFra21-1 level are independent predictors of PFS.	bladder
Melatonin induces cell cycle arrest and suppresses tumor invasion in urinary bladder urothelial carcinoma.	Urinary bladder urothelial carcinoma (UBUC) encompasses about 90% of all bladder cancer cases, and the mainstream treatment is the transurethral resection of the bladder tumor followed by intravesical instillation. High rates of mortality, recurrence, and progression in bladder cancer have stimulated the search for alternative adjuvant therapies. The aim of this study was to investigate the potential of melatonin as adjuvant therapy in bladder cancer. Cell viability and clonogenic ability were assessed by an MTT assay and colony formation. Cell cycle and apoptosis analysis were performed by flow cytometry and Hoechst 33342 staining, while cell metastasis capacity was measured by wound healing and transwell assays. Potential mechanisms were investigated by an oncology array and verified via western blotting. The melatonin treatment significantly reduced T24 and UMUC3 bladder cancer cell proliferation and clonogenic ability. G1 arrest and sub-G1 accumulation in the T24 and UMUC3 cells led to cell proliferation suppression and cell death, and Hoechst 33342 staining further verified the apoptosis induction directly by melatonin. Moreover, melatonin weakened cell motility and invasiveness. Based on the oncology array results, we demonstrated that melatonin exerts its anti-cancer effect by down-regulating the HIF-1α and NF-κB pathways and downstream pathways, including Bcl-2, leading to cell cycle arrest and apoptosis induction in the UBUC cells. Overall, these findings support the potential of melatonin as adjuvant therapy in bladder cancer.	bladder
IMvigor011: a study of adjuvant atezolizumab in patients with high-risk MIBC who are ctDNA+ post-surgery.	The standard-of-care for muscle-invasive bladder cancer is radical surgery with neoadjuvant cisplatin-based chemotherapy. Despite curative intent from these interventions, relapse rates post-surgery remain high, with approximately 50% of patients developing local or distant recurrence within 2 years of surgery and a 5-year survival of only 50-60%. Identifying patients who are high risk for relapse post-surgery is a priority. Monitoring patients for circulating tumor DNA (ctDNA) is a minimally invasive approach that appears attractive for selecting patients potentially suitable for adjuvant treatment with checkpoint inhibitors. IMvigor011 (NCT04660344) is a global, double-blind, randomized phase III study assessing the efficacy of atezolizumab (anti-PD-L1) versus placebo in patients with high-risk muscle-invasive bladder cancer who are ctDNA positive post-cystectomy. The primary end point is disease-free survival in participants who are ctDNA positive within 20 weeks of cystectomy.	bladder